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Biomedical subjects

Stephen F Kemp

Publications and source records attributed to Stephen F Kemp.

16 recordsLinked to original sources
PubMed2006

Investigational agents for the treatment of growth hormone-insensitivity syndrome.

Growth hormone-insensitivity syndrome (GHIS) is usually caused by mutations in the growth hormone receptor. Recombinant IGF-I has been used to treat GHIS either alone (mecasermin) or in combination with IGF-binding protein (IGFBP)-3 (mecasermin rinfabate). IGF-I increases the growth velocity of children with IGF deficiency, which is either as a result of GHIS or an IGF-I gene deletion. Hypoglycaemia has been reported with administration of unbound IGF-I and, in addition, the serum half-life of unbound IGF-I is shorter when administered to patients with GHIS (who have low serum concentrations of its binding protein IGFBP-3) than when administered to normal volunteers or to patients with an IGF-I gene deletion (but normal IGFBP-3 levels). The IGF-I-IGFBP-3 combination was developed to prolong the half-life and counteract the acute adverse events (particularly hypoglycaemia) that are associated with administration of IGF-I. It seems that the IGF-I-IGFBP-3 combination has a longer half-life in patients with GHIS than unbound IGF-I, with fewer reports of adverse events (including hypoglycaemia) when administered to patients with diabetes. There are no studies comparing the efficacy of mecasermin with mecasermin rinfabate; both drugs have been shown to be effective but cannot be differentiated in terms of efficacy.

Child↗
PubMed2006

Efficacy and safety of mecasermin rinfabate.

There has been interest in using recombinant human (rh) insulin-like growth factor (IGF)-I (rhIGF-I) to treat short stature, either alone or in combination with its binding protein (insulin-like growth factor binding protein [IGFBP]-3). IGF-I has been shown to increase growth velocity in children with IGF deficiency, either as a result of growth hormone insensitivity syndrome (GHIS) or IGF gene deletion. However, there have been adverse events, particularly hypoglycaemia, reported with administration of unbound rhIGF-I. In addition, the serum half-life of unbound rhIGF-I is shorter when administered to patients with GHIS, who have low serum concentrations of its binding proteins IGFBP-3 and acid-labile subunit (ALS), than when administered to normal volunteers or to the patient with an IGF-I gene deletion (who had normal levels of IGFBP-3). iPlex (mecasermin rinfabate), an equimolar mixture of IGF-I and its binding protein IGFBP-3, was developed to prolong the half-life and to counteract acute adverse events (particularly hypoglycaemia) associated with administration of IGF-I. Although there are no published data on the efficacy of mecasermin rinfabate in treating growth disorders, it does appear that mecasermin rinfabate has a longer half-life in patients with GHIS than unbound IGF-I, and fewer reports of adverse events (including hypoglycaemia) when administered to patients with diabetes.

Burns↗
PubMed2005

Efficacy and safety results of long-term growth hormone treatment of idiopathic short stature.

CONTEXT: Small clinical trials of GH treatment of idiopathic short stature (ISS) show variable efficacy. OBJECTIVE: The study was an analysis of a large GH registry for efficacy and safety of GH treatment of ISS. There was also a comparison with a specific clinical trial. DESIGN: Up to 7 yr of GH treatment of ISS was evaluated for efficacy and safety in the National Cooperative Growth Study (NCGS). SETTING: The NCGS study was conducted at Genentech, Inc. and included 47,226 patients. PATIENTS: The ISS group included maximum stimulated GH 10 ng/ml or more and/or a report of ISS by investigator (n = 8018; all included for safety). Cohort 1 (n = 2520) was similar to the clinical trial, cohort 2 (n = 283) included subjects younger than 5 yr of age, and cohort 3 (n = 940) was pubertal at GH start. INTERVENTION: GH, approximately 0.30 mg/kg.wk, was given. MAIN OUTCOME MEASURES: These included growth velocities and height sd (HtSDS). RESULTS: Mean first-year growth velocities in cohorts 1, 2, and 3 increased 4.6, 3.9, and 4.4 cm/yr over pretreatment, respectively. Measures included: baseline mean HtSDS, -2.9, -3.2, and -2.8; mean HtSDS at 1 yr, -2.4, -2.3, and -2.3, respectively. Mean HtSDS after 7 yr in cohorts 1 (n = 303) and 2 (n = 85) and 5 yr in cohort 3 (n = 58) were: -1.2, -1.0, and -1.5, respectively. Cohort 3 shorter treatment time was due to advanced baseline age (mean 13.8 yr) and puberty. Mean HtSDS gain in cohort 1 was comparable with the clinical trial. No new safety signals specific to the NCGS ISS population were observed. CONCLUSION: ISS patients in the GH registry demonstrate a significant increase in HtSDS with the safety profile similar to GH-deficient patients. RESULTS were similar to the clinical trial.

Adolescent↗
PubMed2005

Growth hormone treatment of idiopathic short stature: history and demographic data from the NCGS.

Idiopathic short stature (ISS) is a term used to describe children without an identifiable cause for growth failure; these children comprise the largest group of candidates for growth hormone (GH) therapy. Over the past four decades, clinical trials have examined the efficacy and safety of GH treatment in the ISS population; for many of these trials, interpretation of results has been limited by variability in the criteria for ISS, small numbers of subjects, and a short term of study. Recent trials involving larger GH doses for longer periods suggest greater height improvements, but extrapolation to the larger ISS population is still debated. The National Cooperative Growth Study (NCGS) provides an opportunity to evaluate the treatment trends over time. In 1994, there were 20,279 patients enrolled in the NCGS, and 25% were identified as ISS. The most recent analysis was in 2003, and at that time 47,226 patients were enrolled; but only 17% were identified as ISS. This most recent analysis of patients enrolled in the NCGS provides a framework for examining the impact of this new indication for GH on clinical practice patterns.

Clinical Trials as Topic↗
PubMed2005

Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues.

Diabetic osteoporosis is increasingly recognized as a significant comorbidity of type 1 diabetes mellitus. In contrast, type 2 diabetes mellitus is more commonly associated with modest increases in bone mineral density for age. Despite this dichotomy, clinical, in vivo, and in vitro data uniformly support the concept that new bone formation as well as bone microarchitectural integrity are altered in the diabetic state, leading to an increased risk for fragility fracture and inadequate bone regeneration following injury. In this review, we examine the contribution that insulin, as a potential anabolic agent in bone, may make to the pathophysiology of diabetic bone disease. Specifically, we have assimilated human and animal data examining the effects of endogenous insulin production, exogenous insulin administration, insulin sensitivity, and insulin signaling on bone. In so doing, we present evidence that insulin, acting as an anabolic agent in bone, can preserve and increase bone density and bone strength, presumably through direct and/or indirect effects on bone formation.

Animals↗
PubMed2005

SomatoKine: is there a use in treating growth disorders?

Growth hormone (GH) has been used to treat GH deficiency since the late 1950s, and recombinant GH has been available since 1985. GH is also approved to treat non-GH-deficient short stature, such as that seen in Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome, children who are small for gestational age, and idiopathic short stature. There has been interest in using recombinant insulin-like growth factor I (IGF-I) to treat short stature, either alone or in combination with its binding protein, IGF binding protein (IGFBP)-3 (SomatoKine). IGF-I increases growth velocity in children with IGF deficiency, either as a result of growth hormone insensitivity syndrome (GHIS) or IGF-I gene deletion. However, there have been adverse events, particularly hypoglycemia, reported with administration of unbound IGF-I. In addition, the serum half-life of unbound IGF-I is shorter when administered to patients with GHIS, who have low serum concentrations of its primary binding protein IGFBP-3 than when administered to healthy individuals or to patients with an IGF-I gene deletion (who have normal levels of IGFBP-3). SomatoKine was developed to prolong the half-life and to counteract acute adverse events (particularly hypoglycemia) associated with IGF-I administration. SomatoKine appears to have a longer half-life in patients with GHIS than unbound IGF-I and fewer adverse events (including hypoglycemia) have been reported when administered to patients with diabetes.

Growth Disorders↗
PubMed2005

Bisphosphonate treatment of pediatric bone disease.

The science of measuring bone mineral density has developed rapidly and, with it, an improved understanding of the efficacy and safety of various therapeutic interventions in adults. In contrast, the meaning and precision of such measurements in children are equivocal, and the concept of treatment for low bone density in the young patient is still largely undecided. In this report we review the present state of knowledge regarding the use of bisphosphonates during childhood to ameliorate the skeletal abnormalities associated with osteogenesis imperfecta, idiopathic juvenile osteoporosis, fibrous dysplasia of bone and cerebral palsy. Because of the paucity of long-term studies among children regarding the safety and efficacy of these drugs, it is difficult to formulate strong evidence-based recommendations for their use, except perhaps in children with osteogenesis imperfecta.

Bone Density↗
PubMed2004

Fire ant attacks on patients in nursing homes: an increasing problem.

We review the medical reports of fire ant attacks on residents of nursing homes in the context of the medical entomology of these insects, and present recommendations to prevent and manage future attacks. Two reports were recent cases, while a computer-assisted search yielded four other similar cases of attacks by foraging fire ants in the last 10 years. One patient experienced an anaphylactic reaction and 4 patients died within 1 week of the attack. Ants were usually noted in health care facilities days before the attacks. The presence of fire ants around immobile, often cognitively impaired, patients seems to be the primary risk factor for massive fire ant attacks. Health care providers and administrators in fire ant endemic areas must be aware that the presence of fire ants in hospitals and nursing homes represents a hazard. Fire ant infestation can lead to sting attacks on patients, causing respiratory tract obstruction, worsening of pre-existing medical conditions, or frank anaphylaxis. All the attacks reported here have resulted in legal action involving physicians and health care facilities.

Animals↗
PubMed2003

Rhinosinusitis.

History, physical examination, and allergy testing may distinguish the syndromes of rhinitis, classified as allergic, infectious, perennial, nonallergic, and miscellaneous. All may be associated with sinusitis, probably on the basis of obstruction of the osteomeatal complex. Although topical nasal steroids are useful in the treatment of all forms of rhinitis, diagnosis of the offending type in a given patient is necessary for optimal management.

Humans↗
PubMed2003

Near adult heights after growth hormone treatment in patients with idiopathic short stature or idiopathic growth hormone deficiency.

OBJECTIVE: Determination of near adult height (NAH) after recombinant human growth hormone (rhGH) therapy in patients with idiopathic short stature (ISS, maximum stimulated growth hormone [MSGH] > 10 ng/ml) or idiopathic growth hormone deficiency (IGHD, MSGH < or = 10 ng/ml) enrolled in the National Cooperative Growth Study Substudy 2. METHODS: Female NAH was defined as height at age 18 or age 14 plus Tanner stage 4; male NAH was defined as height at age 20 or age 16 plus Tanner stage 4 or 5. RESULTS: Both groups had similar enrollment heights: IGHD -2.7 +/- 0.7 versus ISS -2.8 +/- 0.6 (mean height standard deviation score [SDS] +/- SD). After rhGH treatment, there were no significant differences in NAH between the IGHD and ISS groups (-1.4 +/- 1.0 versus -1.6 +/- 1.0). Enrollment height SDS and MSGH value were significant predictors of delta height for the children with IGHD but not for the children with ISS (R2 = 0.45 IGHD versus R2 = 0.22 ISS). CONCLUSION: We conclude that MSGH values should not be used as the primary criterion for rhGH therapy.

Adolescent↗
PubMed2002

Anaphylaxis: a review of causes and mechanisms.

Anaphylaxis is a life-threatening syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation. Foods and medications cause most anaphylaxis for which a cause can be identified, but virtually any agent capable of directly or indirectly activating mast cells or basophils can cause this syndrome. This review discusses the pathophysiologic mechanisms of anaphylaxis, its causes, and its treatment.

Adrenergic beta-Antagonists↗
PubMed2002

Use of magnetic resonance imaging in short stature: data from National Cooperative Growth Study (NCGS) Substudy 8.

The primary use of magnetic resonance imaging (MRI) in the evaluation of children with short stature (SS) is to discover lesions in the central nervous system (CNS), particularly tumors that may require intervention. MRI has a secondary role in identifying structural abnormalities responsible for growth hormone deficiency (GHD). We examined data from the National Cooperative Growth Study (NCGS) Substudy 8 to determine how American physicians are using MRI in evaluating children with SS. Of the 21,738 short children enrolled in NCGS, 5% underwent MRI during their follow-up. Children who had GH stimulation testing were more likely to have had an MRI than those in whom no GH stimulation test was performed (19% vs 2%, p <0.0001). Moreover, children diagnosed with severe GHD (maximum GH <5 ng/ml) were more likely to have an abnormal finding on MRI. Of these patients, 27% demonstrated an abnormality as compared to 12% and 12.5% in patients with partial GHD and normal GH stimulation test results (>10 ng/ml), respectively. Abnormalities unrelated to the hypothalamus or pituitary represented 30% of these findings, while disorders in pituitary anatomy, including pituitary hypoplasia, pituitary stalk interruption, and ectopic posterior pituitary, represented an additional 30% of abnormal MRI examinations. CNS tumors comprised 23% of abnormal findings in these patients. We conclude that MRI provides significant value in the evaluation of children with SS, by identifying CNS tumors associated with growth failure as well as anatomical abnormalities of the pituitary. These findings are useful in confirming the diagnosis of GHD in children and identifying potential candidates for continued GH replacement in adulthood.

Body Height↗